In the normal heart, the electrical activity, which initiates the subsequent mechanical contraction, is very organized. In general, once one cell is activated, the adjacent cells of the heart will become activated to propagate the electrochemical depolarization associated with systolic contraction of the heart muscle. Unlike skeletal muscle, each heart muscle is electrically connected to its neighbors. This activation usually starts in the right atrium, in the sinoatrial node. From here, the electrical activity spreads across the right and left atrium through either special conduction (i.e., faster pathways) or through normal atrial tissue. To electrically activate the main pumping chambers of the heart, the left and right ventricles, the electrical activity passes through the atrioventricular node. Within this node, the spread of electrical activity is relatively slow. Mechanically, this allows the atrium to contract and pump blood into the ventricles before the ventricles contract.
Following this relatively slow spread of cardiac action potential, the electrical activation travels rapidly down a special conduction pathway, known as the bundle of His. The bundle of His divides into right and left bundle branches; the left dividing in turn into an anterior and posterior branch. This network consists of high-speed conduction fibers, known as the Purkinje fibers. From here, the remaining ventricular muscle cells are activated. This high-speed network is essential for a synchronized contraction of each ventricle relative to associated atria, and for efficient, mechanical synchrony between the left and right ventricles.
Ischemic heart disease and other clinical problems (fibrosis, etc.) can cause conduction delays and/or blockage in this high-speed network. For example, a left bundle branch block leads to late electrical activation of the left ventricular free wall. These conduction problems change the QRS complex in the ECG to a wide QRS complex greater than 120 ms. The corresponding electrical conduction delays cause mechanical dysfunction, decreased cardiac output, as well as valvular regurgitation. Clinical studies have shown early septal circumferential shortening, followed by late stretch as the left ventricular free wall shortenings begins (Kawaguchi M, Murabayashi T, Fetics B J, Nelson G S, Sarmejima H, Nevo E, Kass D A. Quantitation of basal dyssynchrony and acute resynchronization from left or biventricular pacing by novel-contrast variability imaging. Journal of the American College of Cardiology 2002; 39:2052-8). This electrical-mechanical dyssynchrony decreases cardiac output and may cause or exacerbate mitral regurgitation.
The electrical synchrony can be partially restored by biventricular pacing. A pacemaker is implanted in the patient along with a right atrial, right ventricular, and left ventricular lead. The right atrial lead is used to sense the electrical activity in the right atrium and/or to stimulate the right atrium. The pacemaker senses this electrical activity and after a programmable delay (i.e., the delay can be different for each ventricle) electrically stimulates the right and left ventricles, thereby re-establishing electrical synchrony. The leads can be either bipolar or unipolar, and general consist of a coiled conductor, which is electrically isolated from the surrounding tissue. Numerous materials, such as platinum or tantalum coated MP35N alloy wire, can be used for the conductor. At the distal end, the conductor makes electrical contact with the tissue via an electrode, commonly a ring electrode. The electrode can elude an anti-inflammatory cortico-steroid, such as sodium dexamethasone, to reduce irritation of tissue adjacent to the electrode. Insulation materials such as polyurethane, silicone, and ethylene tetrafluor ethylenefluoropolymer are used. The proximal end is directly connected to the pacemaker through an IS-1 standard connector with a sealing-ring (de Voogt W G, Pacemaker leads: Performance and progress. American Journal of Cardiology 1999; 83:187 D-191D).
Initial clinical trials show that resynchronizaton therapy increases exercise capacity and peak oxygen consumption, increases left ventricular ejection fraction, and decreases left ventricular end-diastolic size: all very positive changes for patients with heart failure. These studies also indicate that left ventricular pacing may be as effective as biventricular pacing (Abraham W T, Fisher W G, Smith A L, Delurgio D B, Leon A R, Loh E, Kocovic D Z, packer M, Clavell A L, Hayes D L, Ellestad M, Messenger J. Cardiac resynchronization in chronic heart failure. New England Journal of Medicine 2002; 346:1845-53).
A major technical and clinical challenge associated with these applications concerns the issue of how to place a left ventricular free wall electrode. A typical location for this left ventricular lead is the lateral left ventricular free wall mid way between the base and apex (Auicchio A, Klein H, Tockman B, Sack S, Stellbrink C, Neuzner J, Kramer A, Ding J, Pochet T, Maarse A, Spinelli J. Transvenous biventricular pacing for heart failure: can the obstacles be overcome? American Journal of Cardiology 1999; 83:136 D-142D.). A specialized left ventricular lead is placed into a distal cardiac vein by way of the coronary sinus through a guiding catheter. For example, the EASYTRACK system (Guidant, Si Paul, Minn.) is a transvenous, coronary venous, unipolar pace/sense lead for left ventricular stimulation. [Purerfellner H, Nesser H J, Winter S. Schwierz T, Hornell H, Maertens S. Transvenous left ventricular lead implantation with the EASYTRACK lead system: The European experience. Am J Cardiol 2000; 86 (suppl):157K-164K.] The lead is delivered through a guiding catheter with a specific design to facilitate access to the ostium of the coronary sinus. This catheter provides pushability by incorporating an internal braided-wire design. The distal end of the catheter features a soft tip to prevent damaging of the right atrium or the coronary sinus. The EASYTRACK lead has a 6 Fr. outer diameter and an open-lumen inner conductor coil that tracks over a standard 0.014-inch percutaneous transluminal coronary angioplasty guidewire. The distal end of the electrode consists of a flexible silicone rubber tip designed to be atraumatic to vessels during lead advancement.
In many patients (i.e., at least 10%), either the lead cannot be placed or complications (e.g., dissection or perforation of the coronary sinus or cardiac vein, complete heart block, hemopericardium, and cardiac arrest) occur (Abraham 2002). Because of these difficulties, the left ventricular lead is sometimes placed through a small thoracotomy (Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, Huth C, Schondube F, Wolfhard U, Bocker D, Krahnefeld O, Kirkels H. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. Journal of the American College of Cardiology 2002; 39:2026-33.).